The present invention relates to amorphous solid of besifloxacin ((R)-(+)-7-(3-amino-2,3,4,5,6,7-hexahydro-1H-azepin-1-yl)-1-cyclopropyl-8-chloro-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), processes of preparing, processes of using, and compositions comprising such solid.
Synthetic antimicrobial agents such as nalidixic acid, piromidic acid, and the like are known as drugs for curing infectious diseases caused by Gram negative microorganisms. They exhibit, however, only deficient effects on intractable diseases such as pseudomoniasis and the like.
On the other hand, quinolone carboxylic acid derivatives substituted with a fluorine atom at 6 position, such as norfloxacin, ofloxacin, and ciprofloxacin, or quinolone carboxylic acid derivatives substituted with a chlorine atom at 8 position have been developed (Japanese Patent Laid-open (ko-kai) Nos. 225181/1986, 90183/1984) and clinically used because of their strong antimicrobial activity.
These conventional synthetic antimicrobial agents had defects of insufficient absorptivity in a living body, providing only low bioavailability, and of a low antimicrobial activity against Gram positive microorganisms.
Therefore, development of antimicrobial agents having strong antimicrobial activity against both Gram positive and Gram negative microorganisms, including resistant bacteria, and superior absorptivity in living bodies has been desired. Recently, besifloxacin ((R)-(+)-7-(3-amino-2,3,4,5,6,7-hexahydro-1H-azepin-1-yl)-1-cyclopropyl-8-chloro-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), a new fluoroquinolone carboxylic acid, was developed and approved for the treatment of bacterial conjunctivitis. Besifloxacin offers some advantages over prior fluoroquinolones against certain types of bacteria.
Active pharmaceutical agents (“APIs”) are often organic molecules, which can exist in different organic solid-state forms depending on their processes of manufacture. Such different solid-state forms can have practical influence on pharmaceutical compositions comprising these APIs, such as their processability, physical, chemical, and/or pharmacokinetic properties, stability, etc.
Therefore, it is desirable to provide a solid-state form of besifloxacin that has advantageous properties. In particular, it is very desirable to provide a solid-state form of besifloxacin that has advantageous properties for the manufacture of novel anti-infective pharmaceutical compositions.